DESCRIPTION: Premenstrual syndrome (PMS) is a complex, chronic, menstrually-related disorder, which is reported at severe levels that impairs functioning by 5-10 percent of reproductive-age women. Severe PMS is associated with diminished productivity, lost work time in the prime years of life, and troubled interpersonal relationships, particularly with the partner and children. Only in recent years, and resulting from these studies and other research, has there been scientific information on the efficacy and safety of treatments and investigation of the etiology of PMS. The investigators conceptualize PMS as mood and behavioral changes that derive from central effects, possibly an altered central nervous system (CNS) sensitivity involving changes of gonadal-adrenal steroids. Building on findings of serotonergic involvement in PMS symptoms, the investigators propose to complete and extend studies of the efficacy and safety of serotonergic antidepressant treatment for PMS. The aims of this competing renewal application are to: 1) complete a large clinical study comparing the efficacy of a serotonergic and a noradrenergic antidepressant with a sample size sufficient for definitive results; 2) conduct a randomized, double-blind, placebo-controlled study of intermittent dosing with sertraline administered in the symptomatic premenstrual phase compared to daily dosing; and 3) examine the impact of PMS on functioning, productivity, health care utilization and quality of life before and after medical treatment in aim #1.